The gene encoding the nuclear phosphoprotein p53 is a frequent target of mutation in a wide variety of human tumors. The wild-type p53 protein encoded for the normal p53 gene exhibits a potent growth-suppressing activity which is absent from mutant forms of the protein. Recent studies have shown that p53 proteins can exert both positive and negative effects on gene expression. The ability of the wild-type p53 protein to modulate gene expression has been linked to its growth-suppressing activity. We have previously demonstrated that overexpression of wild- type p53 protein is correlated with down-regulation in the expression of the endogenous growth-regulated genes encoding proliferating cell nuclear antigen (PNCA), B-identification of p53-responsive elements and the characterization of nuclear protein components that collaborate with p53 in modulating the expression of two of these genes; PCNA an DNA polymerase alpha. Information obtained from this study will increase out understanding of the mechanisms of P53-mediated regulation of gene expression.